骨肉瘤VEGF、bFGF,TGF-β_1和TAF表达及其与血管生成的关系

Expsession of vascular endothelial cell growth factor, basic fibroblast growth factor, transforming growth factor β 1 and tumor derived adhesion factor in osteosarcoma and its relation to angiogenesis

目的：研究血管内皮生长因子（ＶＥＧＦ）、碱性成纤维细胞生长因子（ｂＦＧＦ）、转化生长因子－β１（ＴＧＦ－β１）及其受体和肿瘤源性粘附因子（ＴＡＦ）在骨肉瘤中的表达特点，以及它们与肿瘤内微血管密度和病人预后的关系。方法：应用免疫组化和形态计量检测８０例骨肉瘤微血管密度（ＭＶＤ），ＶＥＧＦ、ｂＦＧＦ、ＴＧＦ－β１及其受体和ＴＡＦ的表达，并应用ＣＯＸ比例风险模型检测上述因素和预后的关系。结果：８０例骨肉瘤中，ＶＥＧＦ／ＫＤＲ强阳性４２例（５２．５％），ｂＦＧＦ／ｂＦＧＦｒ阳性４６例（５７．５），ＴＧＦβ１／ＴＧＦβ（ＲＩ）阳性３１例（３８．８％），ＴＡＦ阳性３６例（４５％）。血管生成因子与其受体表达具有一致性，并与ＭＶＤ值显著相关。ＣＯＸ比例风险模型分析结果显示ＭＶＤ和ＶＥＧＦ是影响骨肉瘤的重要因素（Ｐ＜０．０５）。结论：ＶＥＧＦ、ｂＦＧＦ、ＦＧＦ－β１和ＴＡＦ是骨肉瘤血管生成的重要因子，并通过促进血管生成影响病人的预后。其中ＭＶＤ和ＶＥＧＦ是评估骨肉瘤病人预后的重要指标。

Objective: To investigate the expression of vascular endothelial cell growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor β 1 (TGF β 1) and tumor derived adhesion factor (TAF) in osteosarcoma and its relation to neovasculariztion and prognosis of the disease. Methods: The intratumoral microvessel density (MVD) and expression of VEGF, bFGF, TGF β 1 and TAF were determined in 80 cases of osteosarcoma with immunohistochemistry and morphometry. The relationship between the expression of the angiogenic factors and prognosis of the disease was evaluated with a multivariate analysis using COX proportion hazard model. Results: Of the 80 cases, 42 were strong positive for VEGF/KDR (52.5%), 46 for bFGF/bFGFr (57.5%), 31 for TGF β 1/TGFβ (RI) (38.8%) and 36 for TAF (45%) respectively. The expression of the angioenic factors was coordinated with that of their receptors and significantly correlated with MVD. The multivariate analysis using COX hazard model showed that were the most important indicators in prognosis of the disease. Conclusion: All the four factors are involved in the angiogenesis of osteosarcoma. MVD and VEGF are the most useful parameters to evaluate the prognosis of osteosarcoma.